Cabozantinib S-malate and Nivolumab in Treating Patients With Advanced, Recurrent, or Metastatic Endometrial Cancer

Recurrent Endometrial Carcinoma Clinical Trial

Official title: A Randomized Phase 2 Study of Cabozantinib in Combination With Nivolumab in Advanced, Recurrent Metastatic Endometrial Cancer

Status Active, not recruiting

Clinical Trial Summary

This randomized phase II trial studies how well cabozantinib s-malate and nivolumab work in treating patients with endometrial cancer that has come back (recurrent) or spread to other places in the body (advanced or metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may work better in treating endometrial cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the clinical anti-tumor activity of cabozantinib s-malate (XL184 ([cabozantinib]) and nivolumab based on progression free survival (PFS) in patients with advanced, recurrent or metastatic endometrial cancer previously treated with at least one line of platinum-based chemotherapy compared to patients receiving nivolumab alone.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of XL184 and nivolumab in terms of overall response rate (ORR) compared to nivolumab alone.

II. To evaluate overall survival (OS) of patients receiving XL184 and nivolumab compared to patients receiving nivolumab alone.

III. To evaluate the safety of combination treatment using XL184 and nivolumab in patients with advanced, recurrent metastatic endometrial cancer.

IV. To evaluate correlation between PD-L1 expression, CD3, CD4 and CD8 infiltrates and outcome (PFS, ORR, OS).

V. To compare PD-L1 expression, CD3, CD4 and CD8 infiltrates in the primary tumor (archival tissue) and in the tissue from baseline biopsy.

VI. To assess activity (PFS, ORR and OS) of nivolumab alone or in combination with XL184 according to microsatellite instability (MSI)/mismatched repair (MMR) status.

EXPLORATORY OBJECTIVES:

I. To assess activity (PFS, ORR and OS) of XL184 and nivolumab in patients progressed after previous exposure to anti PD-1, PD-L1 or PD-L2 agents or crossed-over from single agent nivolumab, and in patients with diagnosis of carcinosarcoma.

II. To compare microsatellite (MS) and MMR status, in the primary tumor (archival tissue) and in the tissue from baseline biopsy.

III. To assess the genomic and immune-markers landscape at baseline on tumor tissue and changes in immune landscape in peripheral blood during treatment and correlate with outcome.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28 and nivolumab intravenously (IV) over 30 minutes on days 1 and 15, then on day 1 beginning cycle

5. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood sample collection throughout the study and undergo biopsy at screening and optionally at follow up.

ARM B: Patients receive nivolumab as in Arm A. Patients may cross-over to Arm A at the time of disease progression. Patients undergo CT scan, MRI, and blood sample collection throughout the study and undergo biopsy at screening and optionally at follow up.

In both arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30-37 days, then every 8-12 weeks. ;

Related Conditions & MeSH terms

• Advanced Endometrial Carcinoma
• Carcinoma
• Endometrial Neoplasms
• Metastatic Endometrial Carcinoma
• Recurrence
• Recurrent Endometrial Carcinoma
• Stage III Uterine Corpus Cancer AJCC v8
• Stage IV Uterine Corpus Cancer AJCC v8

• NCT number: NCT03367741
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 16, 2018
• Completion date: December 31, 2024